Devices for performing chemical analysis have in recent years become miniaturized. For example, microfluidic devices have been constructed using microelectronic fabrication and micromachining techniques on planar substrates such as glass, silicon or plastic which incorporate a series of interconnected channels or conduits to perform a variety of chemical analysis such as capillary electrophoresis (CE) and high-performance liquid chromatography (HPLC).
Microfluidic substrates have networks that are connected by channels which have mesoscale dimensions, where at least one dimension is usually between 0.1 microns and 500 microns. Such microfluidic substrates may be fabricated using photolithographic techniques similar to those used in the semiconductor industry, and the resulting devices can be used to perform a variety of sophisticated chemical and biological analytical techniques. Microfluidic analytical technology has a number of advantages, including the ability to use very small sample sizes, typically on the order of nanoliters or less. The substrates may be produced at a relatively low cost, and can be formatted to perform numerous specific analytical operations, e.g., protein separations, fluidic mixing, dispensing, valving, reactions, and detections.
Other applications for microfluidic devices include diagnostics involving biomolecules and other analytical techniques such as micro total analysis systems. Such devices, often referred to in the art as “microchips,” also may be fabricated from plastic, with the channels being etched, machined or injection molded into individual substrates. Multiple substrates may be suitably arranged and laminated to construct a microchip of desired function and geometry. In all cases, the channels used to carry out the analyses typically are of capillary scale dimensions.
To fully exploit the technological advances offered by the use of microfluidic devices and to maintain the degree of sensitivity for analytical techniques when processing small volumes, e.g., microliters or less, connectors which introduce and/or withdraw fluids, i.e., liquids and gases, from the device, as well as interconnect microfluidic devices, are a crucial component in the use and performance of the microfluidic device.
A common technique used in the past involves bonding a length of tubing to a port on the microfluidic device with epoxy or other suitable adhesive. Adhesive bonding is unsuitable for many chemical analysis applications because the solvents used attack the adhesive which can lead to channel clogging, detachment of the tubing, and/or contamination of the sample and/or reagents in or delivered to the device. Furthermore, adhesive bonding results in a permanent attachment of the tubing to the microfluidic device which makes it difficult to change components, i.e., either the microfluidic device or the tubing, if necessary. Thus assembly, repair and maintenance of such devices become labor and time intensive, a particularly undesirable feature when the microfluidic device is used for high throughput screening of samples such as in drug discovery.
Other methods involved introducing liquids into an open port on the microfluidic device with the use of an external delivery system such as a micropipette. However, this technique also is undesirable due to the possibility of leaks and spills which may lead to contamination. In addition, the fluid is delivered discretely rather than continuously. Moreover, the use of open pipetting techniques does not permit the use of elevated pressure for fluid delivery such as delivered by a pump, thereby further restricting the applicability of the microfluidic device.
Microfluid systems typically include reservoirs or wells that are etched into the substrate and connected directly to fluid channels to provide fluids necessary to perform various analytical, separations, or chemical synthesis functions. However, because of size constraints imposed by the substrate, the reservoirs are necessarily limited in volume. Thus, any operation such as serial operations, that consume relatively large volumes of fluid, requires that the reservoirs be filled repeatedly: a task which is onerous task and prone to error. In certain operations, it can also be desirable to change the composition of the solutions running through the microfluid system, which can also be very difficult when employing a system with small reservoirs disposed in a substrate.
As is apparent, there is a need for a device for introducing large quantities of fluids into a substrate from an external source and which can be advantageously used in a number of assay formats for high-throughput applications.